Brief Summary: Monoclonal antibodies, such as pertuzumab and cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving pertuzumab together with cetuximab may kill more tumor cells. This phase I/II trial is studying the side effects and best dose of pertuzumab when given together with cetuximab and to see how well they work in treating patients with previously treated locally advanced or metastatic colorectal cancer

Detailed Description: PRIMARY OBJECTIVES: I. To determine the safety, tolerability, and recommended phase II dose of pertuzumab when administered in combination with cetuximab in patients with cetuximab-refractory locally advanced or metastatic colorectal cancer. II. To evaluate the objective tumor response rate (RR) in patients treated with this regimen. SECONDARY OBJECTIVES: I. To evaluate the median progression-free survival (PFS) of patients treated with this regimen. II. To evaluate the median overall survival (OS) of patients treated with this regimen. III. To evaluate the RR, PFS, and OS in a subgroup of patients who are EGFR-positive by immunohistochemistry. IV. To explore the relationship between skin rash and the efficacy outcomes of RR, PFS, and OS in these patients. V. To explore the relationship between objective tumor response on positron emission tomography (PET) scan after course two and the efficacy outcomes of RR, PFS, and OS in these patients. VI. To explore the relationship between a variety of laboratory correlates and the efficacy outcomes of RR, PFS, and OS in these patients. OUTLINE: This is a multicenter, phase I dose-escalation study of pertuzumab followed by a phase II study. PHASE I: Patients receive pertuzumab IV over 30-60 minutes on day 1. Patients also receive cetuximab IV over 60-120 minutes on days 2, 8, and 15 of course 1 and on days 1, 8, and 15 in all subsequent courses. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. PHASE II: Patients receive treatment as in phase I. Pertuzumab is administered at the recommended phase II dose (determined in phase I). Previously collected tumor tissue samples are analyzed for correlative studies. Samples are analyzed for KRAS mutations via polymerase chain reaction and pyrosequencing; EGFR expression via immunohistochemistry and fluorescent in situ hybridization (FISH); HER receptor and ligand gene expression; and circulating tumor cells. Additional blood samples are collected periodically to isolate circulating tumor cells and are analyzed via FISH analysis. After completion of study treatment, patients are followed at 30 days and then periodically thereafter.