Inclusion Criteria:

• Patients ≥ 18 years of age.
• Histologically documented diagnosis of Stage IV Metastatic Colorectal Cancer with Liver Metastases, refractory or progressive after at least one (1) prior line of therapy that must include a fluoropyrimidine (5-fluorouracil or capecitabine) AND (oxaliplatin OR irinotecan), i.e. FOLFOX, FOLFIRI, XELOX, or XELIRI.
• Documentation of wild type k-Ras expression in the liver lesion.
• At least one measurable site of disease (as defined by Response Evaluation Criteria in Solid Tumors, see Appendix 3), or other response assessment criteria, as appropriate.
• Must have ≥ 1 measurable liver lesion that can be accessed by CT guided biopsy.
• Performance status 0,1, or 2 (ECOG).
• Adequate end organ function, defined as the following:

total bilirubin < 1.5 x ULN, SGOT and SGPT < 2.5 x UNL, creatinine < 1.5 x ULN, ANC > 1.5 x 10^9/L, platelets > 100 x 10^9/L.

• Life expectancy of at least 3 months.
• Female patients of childbearing potential must have negative pregnancy test within 7 days before initiation of study drug dosing. Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Female patients of reproductive potential must agree to employ an effective barrier method of birth control throughout the study and for up to 7 days following discontinuation of study drug.
• Written, voluntary informed consent.

Exclusion Criteria:

• Patient has received any other investigational agents within 28 days of first day of study drug dosing, unless the disease is rapidly progressing.
• Patient is < 5 years free of another primary malignancy except: if the other primary malignancy is neither currently clinically significant nor requiring active intervention, or if other primary malignancy is a basal cell skin cancer or a cervical carcinoma in situ. Existence of any other malignant disease is not allowed.
• Patient with Grade III/IV cardiac problems as defined by the New York Heart Association Criteria. (i.e., congestive heart failure, myocardial infarction within 6 months of study)
• Female patients who are pregnant or breast-feeding.
• Patient has a severe and/or uncontrolled medical disease (i.e., uncontrolled diabetes, chronic renal disease, or active uncontrolled infection).
• Patient has a known brain metastasis not treated with definitive therapy with stable disease ≥ 4 weeks.
• Patient has known chronic liver disease (i.e., chronic active hepatitis, and cirrhosis).
• Patient has a known diagnosis of human immunodeficiency virus (HIV) infection.
• Patient received chemotherapy within 2 weeks (6 weeks for nitrosourea or mitomycin-C)prior to study entry, unless the disease is rapidly progressing.
• Patient previously received radiotherapy to ≥ 25% of the bone marrow
• Patient had a major surgery within 2 weeks prior to study entry.
• Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.
• Patients intolerant to imatinib mesylate.