Assess the clinical activity of MAC-321 administered IV as a second-line or third-line antineoplastic agent to subjects with advanced colorectal cancer. Clinical activity will be assessed by determining the percentage of subjects exhibiting an objective response (complete plus partial responses). Tumor response will be assessed following modified Response Evaluation Criteria in Solid Tumors (RECIST) guidelines.

Inclusion Criteria:

• Histologic and/or cytologic diagnosis of metastatic or relapsed colorectal cancer at any time during disease but not candidates for surgical resection.
• Prior treatment with at least 1 conventional approved therapeutic regimen.
• Subjects who have failed prior cytotoxic chemotherapy regimens containing irinotecan (CPT-11), 5 fluorouracil (5-FU), and/or oxaliplatin for advanced (relapsed) metastatic colon cancer are eligible

Exclusion Criteria:

• Other chemotherapy, radiotherapy, immunotherapy, or investigational agents within 4 weeks before signing the ICF (6 weeks if the previous chemotherapy included nitrosoureas or mitomycin)
• Prior radiotherapy to >25% of bone marrow
• Prior exposure to MAC-321