The goal of this clinical study is to determine the dosing and safety of labetuzumab govitecan (formerly known as IMMU-130; hMN-14-SN38, antibody-drug conjugate) in participants with colorectal cancer.

Inclusion Criteria:

• Histologically or cytologically confirmed colorectal adenocarcinoma.
• Stage IV (metastatic) disease.
• Previously treated with at least one prior irinotecan-containing regimen for colorectal cancer.
• Adequate performance status (Eastern Cooperative Oncology Group (ECOG) 0 or 1).
• Expected survival > 6 months.
• Carcinoembryonic antigen (CEA) plasma levels > 5 ng/mL.
• Measurable disease by computed tomography (CT) or Magnetic resonance imaging (MRI).
• At least 4 weeks beyond treatment (chemotherapy, immunotherapy and/or radiation therapy) or major surgery and recovered from all acute toxicities.
• At least 2 weeks beyond corticosteroids.
• Adequate hematology without ongoing transfusional support (hemoglobin > 9 g/dL, absolute neutrophil count (ANC) > 1,500 per mm^3, platelets > 100,000 per mm^3).
• Adequate renal and hepatic function (creatinine ≤ 1.5 x IULN, bilirubin ≤ institutional upper limit of normal (IULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x IULN or 5 x IULN if know liver metastases).
• Otherwise, all toxicity at study entry ≤ Grade 1 by National cancer institute common terminology criteria for adverse events (NCI CTC) v4.0.

Exclusion Criteria:

• Women who are pregnant or lactating.
• Women of childbearing potential and fertile men unwilling to use effective contraception during study until conclusion of 12-week post-treatment evaluation period.
• Individuals with Gilbert's disease or known central nervous system (CNS) metastatic disease.
• Individuals with CEA plasma levels > 1000 ng/mL must be approved in advance by the Sponsor.
• Presence of bulky disease (defined as any single mass > 10 cm in its greatest dimension).
• Individuals with active ≥ grade 2 anorexia, nausea or vomiting, and/or signs of intestinal obstruction.
• Individuals with non-melanoma skin cancer or carcinoma in situ of the cervix are eligible, while individuals with other prior malignancies must have had at least a 3-year disease-free interval.
• Individuals known to be human immunodeficiency virus (HIV) positive, hepatitis B positive, or hepatitis C positive.
• Known history of unstable angina, myocardial infarction, or congestive heart failure present within 6 months or clinically significant cardiac arrhythmia (other than stable atrial fibrillation) requiring anti-arrhythmia therapy.
• Known history of clinically significant active chronic obstructive pulmonary disease (COPD), or other moderate-to-severe chronic respiratory illness present within 6 months.
• Infection requiring intravenous antibiotic use within 1 week.
• Other concurrent medical or psychiatric conditions that, in the Investigator's opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations.