Irinotecan-Eluting Beads in Treating Patients With Refractory Metastatic Colon or Rectal Cancer That Has Spread to the Liver

Inclusion Criteria:

* Patients must have a histologically or cytologically confirmed adenocarcinoma of the colon or rectum that is metastatic to the liver and unresectable and for which standard curative measures do not exist or are no longer effective
* Patients must have received prior fluoropyrimidine, oxaliplatin and irinotecan-based therapy for their disease and had progression or intolerance to these agents that resulted in treatment discontinuation
* Liver disease must not be amenable to potentially curative surgical resection
* Patients must have liver-only or liver-predominant disease to be eligible for this study; liver predominant disease is defined dominant metastatic burden in the liver, with extra-hepatic disease that is judged by the investigator as unlikely to be life threatening within 3 months
* Patients must have a patent portal vein as documented by computed tomography (CT), magnetic resonance imaging (MRI), or ultrasound
* Prior radiation therapy is allowed but must have been completed \>= 4 weeks prior to study entry; patients with history of prior radiation to the liver including radio-labeled microspheres cannot take part in this study
* Eastern Cooperative Oncology Group performance status 0 or 1
* Previous surgery or radiofrequency ablation (RFA) to the liver is allowed; patients with history of chemoembolization or radio-labeled microspheres are excluded
* Life expectancy of \>= 12 weeks
* Leukocytes \>= 3,000/μL
* Absolute neutrophil count \>= 1,500/μL
* Platelets \>= 100,000/μL
* Total bilirubin =\< 1.5 X upper limit of normal (ULN)
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2 X ULN
* Alkaline phosphatase =\< 2 X ULN
* Creatinine =\< 2.0 X mg/dL
* Prothrombin time (PT)/partial thromboplastin time (PTT) =\< 1.5 X ULN
* Women of childbearing potential (WOCBP) and sexually active males must agree to use an accepted and effective method of contraception prior to study entry and for the duration of the study; WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal; women who use oral, implanted or injectable contraceptive hormones, or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy or practicing abstinence or where partner is sterile (e.g., vasectomy) should be considered to be of child bearing potential
* Patients must demonstrate ability to understand and the willingness to sign a written informed consent document
* Patients must discontinue any medication that causes strong cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) induction 2 weeks prior to treatment initiation; patients who are not able to discontinue these drugs are considered ineligible
* Patients must discontinue any medication that causes a strong CYP3A4 inhibition 1 week prior to treatment initiation; patients who are not able to discontinue these drugs are considered ineligible

Exclusion Criteria:

* Patients who have had chemotherapy (including targeted therapy i.e. cetuximab, panitumumab) or radiotherapy =\< 4 weeks or treatment with bevacizumab =\< 6 weeks prior to entering the study or those who have not recovered from acute adverse events due to agents administered more than 4 weeks earlier, with the exclusion of alopecia or neuropathy; patients with history of radiation to the liver including radio-labeled microspheres at any point in their past will be excluded
* Patients may not be receiving nor have received any other investigational agent =\< 4 weeks prior to study registration
* Pregnant or nursing women may not participate in this trial
* Patients with known brain metastases are excluded from this study
* Known human immunodeficiency virus (HIV)-positive patients and those with known hepatitis B or C are excluded from the study
* Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active bacterial infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
* Patients with clinically evident ascites requiring medical management or paracentesis, or Childs-Pugh score B/C are not eligible
* Patients with evidence of other cancer within 5 years, excluding adequately treated basal cell carcinoma of the skin
* Patient with significant cardiac, renal or hematologic or pulmonary dysfunction
* Patients with previous chemoembolization to liver metastases