Inclusion Criteria:

1. Ability to understand and willingness to sign a written informed consent (includes willingness to avoid physical intimacy during and for 2 weeks post NV1020 treatment)
2. 18 years or more of age
3. Colorectal adenocarcinoma histologically confirmed within one year prior to enrollment in the study
4. Liver dominant metastases (CT-measurable lesions with less than 50% total liver involvement), histologically confirmed
5. Failed conventional chemotherapy for metastatic disease
6. Candidate for additional chemotherapy
7. Karnofsky Performance Status 70% or greater
8. Life expectancy greater than or equal to 4 months, based on the investigator's opinion
9. Seropositive for herpes simplex virus-1 (HSV-1)
10. Fecund females: negative for pregnancy test (urine or serum)
11. Effective double-barrier contraception for a minimum of 2 months following final infusion of NV1020

Exclusion Criteria:

1. Dominant extrahepatic disease, including cerebral metastases, significant malignant ascites or other extrahepatic metastases that are symptomatic, in critical locations or otherwise likely to confound NV1020 evaluations, in the opinion of the investigator
2. Seronegative for HSV-1

3. Significant active/unstable non-malignant disease or laboratory test (hematology and chemistry) results that meet any of the following:

   • White blood cell count (WBC) less than or equal to 3 x 10e3/mm3
   • Absolute neutrophil count (ANC) less than or equal to 1.5 x 10e3/mm3
   • Platelets less than or equal to 100,000/mm3
   • Hemoglobin (Hgb) less than or equal to 9.0 g/dL
   • Prothrombin time/partial thromboplastin time (PT/PTT) > upper limit of normal (ULN)
   • Serum creatinine > 2.0 mg/dL
   • AST or ALT > 2.5 times ULN or total bilirubin > 1.5 times ULN
   • Alkaline phosphatase > 2.5 times ULN
4. Chemotherapy < 4 weeks prior to the first NV1020 infusion (mitomycin or nitrosurea < 6 weeks)
5. Immunotherapy < 6 weeks prior to the first NV1020 infusion
6. Radiotherapy (external or internal) to the liver
7. Major surgery (excluding pump placement and cholecystectomy) less than or equal to 2 weeks prior to the first NV1020 infusion and the patient must be clinically stable. Pump placement and cholecystectomy less than or equal to 1 week prior to the first NV1020 infusion
8. Female who is pregnant or nursing
9. Patients wishing to conceive within 2 months after the last infusion of NV1020
10. Any investigational agent administered less than or equal to 4 weeks prior to NV1020 infusion
11. Acute HSV infection requiring systemic antiviral therapy or history of serious HSV infection (e.g., ocular, encephalitic, etc.)
12. Active viral hepatitis (evidence for infection with hepatitis A, B or C viruses)
13. Known infection with HIV
14. Known hypersensitivity to any component of the NV1020 formulation
15. History of, or current, bleeding or coagulation disorder
16. History of significant hepatic fibrosis, cirrhosis, or hemachromatosis
17. History of malignancy other than colorectal cancer, within 5 years prior to start of study participation, with the exception of in situ cervical or skin carcinoma
18. Active severe infection and any other concurrent disease or medical conditions that are likely to interfere with the study, as judged by the investigator
19. Systemic corticosteroid administration < 4 weeks prior to starting NV1020 treatment
20. Prior treatment with NV1020 or other putative oncolytic viruses