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)

- ECOG 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

- Severe or unstable cardiac disease

- Viable 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

- Pregnant or nursing an infant

- Diagnosis of chronic inflammatory bowel disease and/or bowel obstruction.