Inclusion Criteria:

Patients must fulfill all of the following criteria to be eligible for study entry:

• Age 18-80
• Able to provide informed consent
• Biopsy proven unresectable metastatic adenocarcinoma of the colon or rectum
• Documented progression on prior first-line oxaliplatin-based or irinotecan-based regimen for metastatic colorectal cancer
• Radiographically measurable disease with at least one bidimensionally measurable lesion of > 1 cm
• Prior first-line regimen must have been completed at least 4 weeks prior to study treatment
• Use of biologic agents with first-line chemotherapy permitted
• Previous adjuvant regimens must have been greater than 6 months before inclusion
• Adequate organ function including bone marrow, liver and renal function as defined by the following values: absolute neutrophil count > 1500/uL; Hgb > 9 g/dL; platelets > 90,000/uL; INR < 1.8 (unless in therapeutic range if taking warfarin or other warfarin-derivative anticoagulants and are being monitored regularly for changes in prothrombin time or INR); bilirubin < 2X ULN; alkaline phosphatase < 3X ULN; AST/ALT < 5X ULN; serum creatinine < 1.5 X ULN
• ECOG status < 2

Exclusion Criteria:

Patients meeting any of the following criteria are ineligible for study entry:

• Prior second-line chemotherapy regimens for colorectal cancer
• Prior treatment with erlotinib or gefitinib
• CNS metastasis
• Second malignancies less than 5 years prior to enrollment. Completely resected basal or squamous cell carcinoma of the skin is allowed.
• Untreated/unresolved bowel obstruction
• Inability to take oral mediations
• HIV positive
• Pregnancy
• Other uncontrolled medical illnesses
• Current diarrhea > grade 2
• Symptomatic angina or uncontrolled congestive heart failure