Combination Chemotherapy and Cetuximab or Bevacizumab in Treating Patients With Metastatic Colorectal Cancer

Inclusion Criteria:

* Patients must have histologically confirmed colon or rectal cancer that has metastasized; no biopsy of metastatic site(s) are required if presentation is consistent with metastatic disease
* Available archived tissue block or slides from the primary colon or rectal cancer; approximately 25 slides from the primary tumor tissue are necessary for testing of all markers
* Patients must have measurable disease by RECIST 1.1, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>= 10 mm with computed tomography (CT) scan or clinical exam with calipers; lymph nodes must be 15 mm in shortest dimension as measured on CT scan
* Patients may not have received prior therapy for metastatic colorectal cancer; prior adjuvant therapy (including any of the study agents) is permitted if completed \> 6 months from the initial detection of metastatic disease
* Eastern Cooperative Oncology Group (ECOG) performance status 0-1
* Absolute neutrophil count \>= 1,500/mcL
* Platelets \>= 100,000/mcL
* Total bilirubin =\< 2 X institutional upper limit of normal (ULN)
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/ alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase \[SGPT\]) =\< 3 X institutional ULN or =\< 5 X ULN if known liver metastases
* Creatinine clearance \>= 50 mL/min (as calculated by Cockroft and Gault formula)
* Urine protein:creatinine (UPC) ratio \< 1.0 at screening (as calculated from urine protein concentration and urine creatinine concentration); patients with a UPC ratio \>= 1 will undergo a 24-hour urine collection, which must be adequate and demonstrate \< 1 gram in order to participate
* Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

* Patients who have had previous chemotherapy for metastatic colorectal cancer
* Uncontrolled hypertension (\>150/100 mmHg) despite a stable regimen of anti-hypertensive medication
* History of cardiovascular disease, defined as previous myocardial infarction, cerebrovascular accident, uncontrolled congestive heart failure (New York Heart Association \> Class II), clinically significant ventricular arrhythmia requiring medication, clinically significant peripheral vascular disease, or unstable angina within 6 months of study enrollment
* Underlying neuropathy \>= grade 2
* Serious non-healing wounds, ulcers, or fistulas
* Major surgery, open biopsy, or major traumatic injury within 28 days of registration, or anticipation of need for surgical procedure during course of study, and core biopsy or fine needle aspiration within 7 days of registration; closed biopsy or access port placement is acceptable
* A history of thrombotic or hemorrhagic disorder; patients with elevated international normalized ratio (INR) (2.0 to 3.0) on stable doses of therapeutic anticoagulation are eligible
* Untreated brain metastases; patients with treated brain metastases who have completed radiation therapy, are clinically and radiographically stable, and are off steroid therapy may be enrolled
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to cetuximab, oxaliplatin, capecitabine, or other agents used in the study
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements
* Pregnant women are excluded; breastfeeding should be discontinued if the mother is treated with chemotherapy
* Human Immunodeficiency Virus (HIV)-positive patients on combination antiretroviral therapy are ineligible; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
* Patients must not have a history of another neoplasm \< 5 years prior to enrollment, except for non-metastatic, non-melanoma skin cancer or carcinoma in situ of the cervix
* Patients of child-bearing potential who are unwilling or unable to utilize contraceptive measures including barrier contraception