Phase III Trial of Irinotecan-Based Chemotherapy Plus Cetuximab (NSC-714692) or Bevacizumab (NSC-704865) as Second-Line Therapy for Patients with Metastatic Colorectal Cancer who have Progressed on Bevacizumab with either FOLFOX, OPTIMOX, or XELOX

Histologically or cytologically confirmed metastatic colorectal cancer. Must have wild type KRAS. Must have progressed on first-line chemotherapy with bevacizumab plus either FOLFOX, OPTIMOX, or XELOX within 90 days after last bevacizumab dose and within 28 days prior to registration. Pts who discontinued oxaliplatin, continued with 5-FU/LV or capecitabine and bevacizumab and then had subsequent progression while on fluoropyrimidine and bevacizumab are eligible. Pts who discontinued bevacizumab due to adverse events in the first-line setting are not eligible. Measurable and/or non-measurable disease. Exams for measurable dz must have been completed within 28 days prior to reg. Exams for non-measurable dz must have been completed within 42 days prior to registration. At least 14 days must have elapsed since the last dose of first line chemotherapy and bevacizumab. Must not have received prior irinotecan (either as adjuvant or metastatic tx). No prior tx with cetuximab or other agents targeting VEGF or EGFR (except for bevacizumab). At least 28 days must have elapsed since any radiation tx or major surgery, and all adverse events or related effects must be resolved. Zubrod 0-2. Within 28 days prior to reg: ANC >/= 1,500/mcl; platelets >/= 100,000/mcl; hemoglobin >/= 9 g/dl; total bilirubin </= 1.5xIULN; SGOT or SGPT </= 2.5xIULN (if liver mets, SGOT or SGPT </= 5xIULN); serum creatinine </= IULN or measured or estimated creatinine clearance >/= 60 ml/min. No history or known presence of brain mets. Pts may be on full dose anticoagulation with warfarin provided that they have acceptable INR (between 2 and 3), obtained within 28 days prior to registration. Pts may receive low molecular weight heparin. No clinically relevant bleeding diathesis or coagulopathy (except as mentioned above). Must not have had nephritic range proteinuria from prior bevacizumab tx. Urine protein must be screened by urine analysis for UPC ratio. For UPC ratio > 0.5, 24-hour urine protein must be obtained and the level must be <1,000 mg. Urine protein and creatinine used in calculating the UPC ratio must be obtained within 28 days prior to reg. No uncontrolled high blood pressure (SBP>150 and DBP>90 mmHg) obtained within 28 days prior to reg. No arterial thrombosis, unstable angina, MI or CVA within 6 months prior to reg. No congestive heart failure >/= Grade 2. No unstable symptomatic arrhythmia requiring medication. No clinically significant peripheral vascular disease. No serious or non-healing active wound ulcer or bone fracture. No history of GI perforation while on previous bevacizumab. Pts with history of significant bleeding episodes within 6 months prior to reg are not eligible unless the source of bleeding has been resected. No known hypersensitivity to bevacizumab or known potential hypersensitivity to cetuximab. Age >/= 18 years. No plans to receive concurrent chemotherapy, hormonal therapy, radiotherapy, immunotherapy or any other type of therapy for tx of cancer while on this protocol treatment. Not pregnant or nursing. No prior malignancy except adequately treated basal (or squamous cell) skin cancer, in situ cervical cancer or other cancer for which the patient has been disease free for five years.