Inclusion Criteria:

- Histologically-confirmed, advanced/metastatic colorectal carcinoma

- Failed both oxaliplatin and irinotecan based regimens for advanced/metastatic disease
(tumor progression on or within 3 months of treatment completion)

- Erbitux therapy resistant: Ras mutant tumor status, and/or failed Erbitux therapy
(tumor progression on or within 3 months of treatment completion or Erbitux treatment
not indicated due to lack of epidermal growth factor (EGFR) expression)

- At least one measurable tumor mass by PET-CT/CT/MRI (lesion that can accurately be
measured in at least one dimension with longest diameter > 1 cm)

- Expected survival for approximately 12 weeks or longer

- Karnofsky Performance Score (KPS) ≥ 70

- Age ≥18 years

- WBC ≥ 3,500 cells/mm3 and ≤ 50,000 cells/mm3

- ANC ≥ 1,500 cells/mm3

- Hemoglobin ≥ 10 g/dL (transfusion allowed)

- Platelet count ≥ 100,000 plts/mm3

- Total bilirubin ≤ 1.5 ULN

- AST, ALT ≤2.5 ULN (if liver metastases(+): AST,ALT ≤5.0 x ULN)

- Serum chemistries within normal limits (WNL) or Grade 1 (excluding alkaline
phosphatase) - If patients are diabetic or have a screening random glucose > 160
mg/dL, a fasting glucose must be done and patients must be WNL or Grade 1 in order to
be eligible for the study.

Exclusion Criteria:

- Significant immunodeficiency due to underlying illness (e.g. HIV/AIDS) and/or
medication (e.g. systemic corticosteroids)

- Known myeloproliferative disorders requiring systemic therapy

- History of exfoliative skin condition (e.g. eczema or ectopic dermatitis) requiring
systemic therapy

- History of acquiring opportunistic infections.

- Tumor(s) invading a major vascular structure (e.g. carotid artery)

- Tumor(s) in location that would potentially result in significant clinical adverse
effects if post-treatment tumor swelling were to occur (e.g. tumors impinging on the
upper airway or affecting biliary tract drainage, etc.)

- Clinically significant and/or rapidly accumulating ascites, peri-cardial and/or
pleural effusions

- Severe or unstable cardiac disease, including (for example) coronary artery disease
requiring increased doses of anti-anginal mediation and/or coronary angioplasty
(including stent placement) within the preceding 24 months

- Current, known CNS malignancy (history of completely resected or irradiated brain
metastases by WBRT or stereotactic radiosurgery allowed)

- Received anti-cancer therapy within 4 weeks prior to first treatment (6 weeks in case
of mitomycin C or nitrosoureas)

- Use of anti-viral, anti-platelet, or anti-coagulation medication [Patients who
discontinue such medications within 7 days prior to first treatment may be eligible
for this study.] Low dose aspirin (approximately 81 mg) allowed.

- Pulse oximetry O2 saturation <90% at rest

- Experienced a severe systemic reaction or side-effect as a result of a previous
smallpox vaccination

Household contact exclusions:

- Women who are pregnant or nursing an infant

- Children < 12 months old

- People with skin disease (e.g. eczema, atopic dermatitis, and related diseases
Immunocompromised hosts (severe deficiencies in cell-mediated immunity, including
AIDS, organ transplant recipients, hematologic malignancies)Patients with household
contacts meeting any of the above criteria will be excluded unless alternate living
arrangements can be made during the patient's dosing period and for at least 7 days
following the last dose of study medication.