Hepatic Artery Infusion Pump Chemotherapy With Floxuridine and Dexamethasone in Combination With Systemic Chemotherapy for Patients With Colorectal Cancer Metastatic to the Liver

* INCLUSION CRITERIA:
* Patients must have histologically or cytologically confirmed diagnosis of colorectal adenocarcinoma.
* Patients must have measurable liver metastatic disease.
* Patients must have progressed on, been intolerant of or have residual disease after oxaliplatin- or irinotecan-containing, fluorouracil-based, chemotherapeutic regimen.
* Age greater than or equal to 18 years.
* Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 1
* Patients must have adequate organ and marrow function as defined below:

  * leukocytes \> 3,000/mcL
  * absolute neutrophil count \> 1,500/mcL
  * platelets \> 90,000/mcL
  * total bilirubin \< 1.5 X institutional upper limit of normal
  * Aspartate aminotransferase (AST) Serum glutamic oxaloacetic transaminase (SGOT)/Alanine transaminase (ALT) Serum glutamic-pyruvic transaminase (SGPT) \< 2.5 X institutional upper limit of normal
  * creatinine within normal institutional limits OR estimated glomerular filtration rate (eGFR) within normal as predicted by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation \> 60 mL/min/1.73 m\^2.
* The hepatic artery infusion pump chemotherapy has potential teratogenic and/or abortifacient effects. For this reason, 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, for the duration of study participation and after completion of study treatment : 3 months after the last study drug for men; 6 months after the last study drug for women. 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.
* Arterial anatomy on computed tomography (CT) angiogram amenable to placement of the Hepatic Artery Infusion Pump (HAIP).
* Ability of subject to understand and the willingness to sign a written informed consent document.
* Human immunodeficiency virus (HIV)-positive patients may be considered for this study only after consultation with an HIV trained physician.
* Patients must agree to co-enroll on the Surgical Oncology Programs tissue collection protocol 13C0176, 'Tumor, Normal Tissue and Specimens from Patients Undergoing Evaluation or Surgical Resection of Solid Tumors'

EXCLUSION CRITERIA:

* Patients with liver metastases amenable to resection to No Evidence of Disease (NED) in one stage.
* Patients who are receiving any other investigational agents.
* Patients with incontrovertible radiographic evidence of disease outside of the colon/rectum (primary) and liver given unlikelihood of benefit from liver-directed therapy.

Note: The exception to this exclusion is patients with fewer than five lung lesions greater than 1 cm that have not increased in size by more than 10% over a 4-month period of time, and are amenable to resection should subsequent problematic growth occur. Lesions less than 1 cm are indeterminant as far as etiology is concerned and will be ignored. Patients with liver metastases and oligometastatic lung lesions (we define oligometastatic as less than 5 amenable to thoracoscopic removal) are still likely to benefit from liver directed therapy.

* Patients who have undergone extra-hepatic metastasectomy and have a documented disease-free interval less than or equal to 4 months.
* Microsatellite Instability (MSI)-high patients who need to be treated with check-point inhibitors
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. This also includes any condition, including the presence of laboratory abnormalities, which in the opinion of the Principal Investigator places the subject at unacceptable risk if they were to participate in the study or confounds the ability to interpret data from the study.
* Active concurrent malignancies within the last five years other than colorectal primary except basal cell skin carcinoma and thyroid carcinoma.
* Prior radiation to liver.
* Pregnant women are excluded from this study because of the potential for teratogenic or abortifacient effects of the HAIP chemotherapy. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with HAIP, breast-feeding should be discontinued if the mother is treated. These potential risks may also apply to other agents used in this study. Lactating women must-not breastfeed during study treatment and until at least 7 days after the final dose of study drug(s).
* Patients with active Hepatitis B or C infection because of the potential for increased liver toxicity given the damaging effects of the virus.
* History of allergic reactions attributed to compounds of similar chemical composition to floxuridine (FUDR) or heparin.