Recombinant Vaccinia Virus Administered Intravenously in Patients With Metastatic, Refractory Colorectal Carcinoma

Inclusion Criteria: * Histologically-confirmed, advanced metastatic colorectal cancer failed treatment with fluoropyrimidine (fluoruracil or capecitabine) and oxaliplatin based therapies or had contradictions to treatment with these drugs as determined by the investigator * Failed treatment with irinotecan * Kras mutant tumor or Kras wild-type having failed cetuximab (Erbitux) or panitumumab (Vectibix) or had contradictions to treatment * Regorafenib-naïve (have not received regorafenib) * Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1 or 2 * Measurable tumor (≥1 cm longest diameter) * Acceptable health status as determined by the investigator and blood work (Chemistry, Complete Blood Count, Coagulation) Exclusion Criteria: * Intolerant to Irinotecan (if assigned to the combination arm: Cohort 3, Cohort 4 or Combination Expansion Arm) * Treatment with ketoconazole, enzyme-inducing anticonvulsants and St. John's Wort (if assigned to combination arm) * Significant immunodeficiency due to underlying illness and/or medication * History of severe exfoliative skin condition requiring systemic therapy within the past 2 years * Clinically significant and/or rapidly accumulating ascites, pericardial and/or pleural effusions * Active cardiovascular disease, including but not limited to significant coronary artery disease (e.g., requiring angioplasty or stenting) or congestive heart failure within the preceding 12 months * Viable Centrual Nervous System (CNS) malignancy associated with clinical symptoms * Received anti-cancer therapy within 4 weeks prior to first treatment (6 weeks for mitomycin c or nitrosoureas) * Prior participation in any other research protocol involving an investigational medicinal product within 4 weeks prior to first treatment * Use of prohibited anti-viral medication, interferon/pegylated interferon (PEG-IFN) or ribavirin that cannot be discontinued within 14 days prior to any JX 594 dose * Inability to suspend treatment with anti-hypertensive medication for 48 hours prior to and 48 hours after all JX-594 treatments. * Pregnant or nursing an infant * Diagnosis of chronic inflammatory bowel disease and/or bowel obstruction.