Standard of Care Alone or in Combination With Ad-CEA Vaccine and Avelumab in People With Previously Untreated Metastatic Colorectal Cancer QUILT-2.004

* INCLUSION CRITERIA:
* Subjects must have previously untreated metastatic or unresectable colorectal cancer and have no contraindications to treatment with the standard of care regimen as determined by the investigator. Prior adjuvant therapy for surgically resectable disease (including oligometastatic disease) is acceptable (including immunotherapy) but must have been completed at least 6 months prior to enrollment.
* Patients should not be eligible for potentially curative surgical intervention in the case of oligometastatic disease at the time of enrollment or must have actively refused after explicit discussion of potential benefit of this intervention with multidisciplinary team.
* Histologically confirmed colorectal cancer
* Patients must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
* Age greater than or equal to 18 years. Because safety data is not known with this agent in patients less than 18 years old, children are excluded from this study.
* Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.
* Patients must have normal organ and marrow function as defined below:

  * Creatinine clearance (per Institutional standard or 24-hour urine) greater than or equal to 30 mL/min.
  * Adequate hepatic function defined by a total bilirubin level less than or equal to 1.5 the upper limit of normal range (ULN), an aspartate aminotransferase (AST), level less than or equal to 2.5 ULN, and an alanine aminotransferase (ALT) level less than or equal to 2.5 ULN or, for subjects with documented metastatic disease to the liver, AST and ALT levels less than or equal to 5 ULN.
  * Hematological eligibility parameters (within16 days of enrollment):
  * Granulocyte count greater than or equal to 1,500/mm\^3
  * Platelet count greater than or equal to 100,000/mm\^3
  * Hemoglobin greater than or equal to 9 g/dL
* The effects of Ad-CEA vaccine and Avelumab on the developing human fetus are unknown. For this reason and because Ad-CEA vaccine and Avelumab as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and for a period of 4 months after the last treatment with avelumab or 6 months after the last administration of bevacizumab, whichever occurs later. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
* Ability of subject to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA:

* Metastatic or unresectable colorectal cancer with mismatch repair deficiency (MMR-D or microsatellite instability (MSI)-High).
* Concurrent treatment for cancer except agents specified within the treatment protocol.
* Prior surgery or gastrointestinal perforation within 28 days of enrollment.
* Persisting toxicity related to prior therapy (National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade \> 1); however, alopecia, sensory neuropathy Grade \<=2, or other Grade \<=2 AEs not constituting a safety risk based on investigator's judgment are acceptable.
* Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome.
* Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive)
* Any significant disease that, in the opinion of the investigator, may impair the patient's tolerance of study treatment.
* Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible.
* Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses less than or equal to 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., computed tomography (CT) scan premedication).
* Patients who are receiving any other investigational agents within 28 days before start of study treatment.
* Prior organ transplantation including allogenic stem-cell transplantation.
* Subjects with active central nervous system (CNS) metastases causing clinical symptoms or metastases that require therapeutic intervention are excluded. Subjects with a history of treated CNS metastases (by surgery or radiation therapy) are not eligible unless they have fully recovered from treatment, demonstrated no progression for at least 2 months, and do not require continued steroid therapy. Subjects with CNS metastases incidentally detected during Screening which do not cause clinical symptoms and for which standard of care suggests no therapeutic intervention is needed are eligible.
* Active infection, requiring systemic therapy,
* Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (\< 3 months prior to enrollment), myocardial infarction (\< 3 months prior to enrollment), unstable angina, congestive heart failure (greater than or equal to New York Heart Association Classification Class II), or uncontrolled arrhythmias.
* Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
* Pregnant women and breastfeeding mothers are excluded due to unknown impact on embryos or infants.
* Known alcohol or drug abuse.
* Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.03 Grade greater than or equal to 3).
* Patients with a known hypersensitivity/allergy to any of the standard of care agents used in this study or related compounds (e.g., platinum compounds) are excluded.
* Prior history of hypertensive emergency or hypertensive encephalopathy (for those expected to receive bevacizumab.
* Serious, non-healing wound, active ulcer, or untreated bone fracture, including tumor related pathological fracture.
* Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation).
* Patients being treated with medications with drug-drug interactions with study agents will require evaluation by to determine if full doses of all study treatments can be given safely. Significant drug-drug interactions will need to be addressed prior to enrollment. Alternatively, the patient will not be eligible.
* Vaccination within 4 weeks of the first dose of avelumab and while on trials is prohibited except for administration of inactivated vaccines.