Bevacizumab and Cetuximab With or Without Irinotecan in Treating Patients With Irinotecan-Refractory Metastatic Colorectal Cancer

Inclusion Criteria:

* Histologically or cytologically confirmed colorectal cancer

  * Metastatic disease by diagnostic imaging studies
* Measurable disease

  * At least 1 unidimensionally measurable lesion with minimum lesion size at least twice the slice thickness of the imaging study used
* Refractory to irinotecan, evidenced by clinical documentation

  * Received at least 1 prior irinotecan-containing chemotherapy regimen for metastatic disease and progressed during or within 6 weeks after completion of therapy
* Must have received prior irinotecan according to 1 of the following schedules:

  * Weekly administration with a starting dose of 100-125 mg/m\^2
  * Biweekly administration (every other week) with a starting dose of approximately 180 mg/m\^2
  * Once every three weekly administration with a starting dose of 300-350 mg/m\^2
* No known brain metastases
* No prior primary CNS tumors
* Performance status - ECOG 0-1
* Performance status - Karnofsky 80-100%
* More than 3 months
* WBC \>= 3,000/mm\^3
* Absolute neutrophil count \>= 1,500/mm\^3
* Platelet count \>= 100,000/mm\^3
* Hemoglobin \>= 9 g/dL
* No bleeding diathesis or coagulopathy
* Bilirubin normal
* AST and ALT =\< 2.5 times upper limit of normal (ULN) (5 times ULN in the presence of known liver metastases)
* INR \< 1.5 (for patients receiving warfarin)
* Creatinine =\< ULN
* Creatinine clearance ≥ 60 mL/min
* No proteinuria
* No prior stroke
* No symptomatic congestive heart failure
* No unstable angina pectoris
* No uncontrolled hypertension
* No clinically significant cardiac arrhythmia
* None of the following arterial thromboembolic events within the past 6 months:

  * Myocardial infarction
  * Cerebrovascular accident
  * Transient ischemic attack
  * Unstable angina
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for at least 3 months after study participation
* No significant traumatic injury within the past 28 days
* No grade 3 or greater neurotoxicity
* No uncontrolled seizures
* No prior allergic reactions attributed to compounds of similar chemical or biological composition to study agents
* No prior irinotecan intolerance
* No ongoing or active infection requiring parenteral antibiotics
* No serious nonhealing active wound, ulcer, or bone fracture
* No psychiatric illness or social situation that would preclude study compliance
* No other concurrent uncontrolled illness that would preclude study participation
* No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
* No prior cetuximab
* No other prior epidermal growth factor receptor-directed therapy
* No prior anticancer murine or chimeric monoclonal antibody therapy

  * Prior humanized monoclonal antibody therapy allowed
* No prior bevacizumab
* No other prior vascular endothelial growth factor-targeted therapy
* More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
* More than 4 weeks since prior radiotherapy
* More than 28 days since prior major surgical procedure or open biopsy
* Recovered from all prior therapy
* Any number of prior standard or investigational regimens allowed
* No other concurrent investigational agents
* No other concurrent anticancer therapy
* No recent or concurrent thrombolytic agents
* No recent or concurrent full-dose warfarin except as required to maintain patency of preexisting, permanent indwelling IV catheters
* No concurrent therapeutic heparin

  * Concurrent prophylactic low-molecular weight heparin allowed
* No concurrent chronic daily aspirin (\> 325 mg/day)
* No concurrent nonsteroidal anti-inflammatory medications known to inhibit platelet function
* No concurrent combination antiretroviral therapy for HIV-positive patients