Inclusion Criteria:

1. Patients must have histologically or cytologically confirmed adenocarcinoma of the colon or rectum. Histology from the hepatic metastasis is not mandatory if the morphological appearances on cross sectional imaging and tumor markers (CEA) are indicative of a colorectal primary.
2. Patients must have measurable disease, defined as at least one lesion that can be accurately measured in two dimensions (longest diameter to be recorded) as greater than or equal to 20 mm with conventional techniques or as greater than or equal to 10 mm with spiral CT scan.
3. Patients must have radiological evidence of disease progression of disease within 6 months of their most recent dose of chemotherapeutic regimens that should include irinotecan.
4. Age greater than or equal to 18 years.
5. ECOG performance status less than or equal to 2.
6. Patients must have normal organ and marrow function as defined below within 30 days of receiving the investigational agent: - leukocytes greater than or equal to 3,000/mL - absolute neutrophil count greater than or equal to 1,500/mL - platelets greater than or equal to 100,000/mL - total bilirubin less than or equal to 1.5 times upper limits of normal institutional limits - AST(SGOT) less than or equal to 2.5 X 46 IU/L and ALT(SGPT) less than or equal to 2.5 X 56 IU/L - Creatinine less than or equal to 1.5 times upper limits of normal institutional limits
7. Patients with a prior history of non-colorectal cancer who have no active disease may be eligible if they are disease free for greater than or equal to 12 months prior to treatment.
8. The effects of SIR-Spheres, irinotecan or cetuximab on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because radiation as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while in this study, she should inform her treating physician immediately.
9. Ability to understand and the willingness to sign a written informed consent document.
10. Patients without evidence of local disease recurrence from colorectal cancer are eligible
11. Patients with extrahepatic disease confined to the lung is permitted if < 4 lesions are depicted on CTand all are < 3 cm in size
12. Patients with brain mets are eligible for this trial if those patients who have had the area surgically resected or irradiated and have no evidence of active disease as demonstrated by MRI of the brain. Patients must have no evidence of residual neurological dysfunction as per baseline neurological exam. Patients with untreated brain metastases will be considered ineligible.

Exclusion Criteria:

1. Patients who have had chemotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier will be excluded. Patients who have had hepatic external beam radiotherapy will be excluded.
2. Patients may not be receiving any other investigational agents.
3. History of allergic reactions attributed to compounds of similar chemical or biologic composition to SIR-Spheres, irinotecan or cetuximab or other agents used in the study.
4. Evidence of ascites, biopsy proven cirrhosis or portal hypertension suggested by the presence of characteristic imaging features on cross sectional imaging or esophageal varicosities demonstrated on endoscopy or barium swallow. A diagnostic study to rule out the presence of portal hypertension will not be required unless the findings on cross sectional imaging are suggestive but not confirmatory.
5. Hepatic arterial anatomy that would prevent catheterization and the administration of SIR-Spheres into the liver.
6. >20% hepatopulmonary shunting on a Technetium99-MAA nuclear scan
7. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring hospital admission or antibiotics,symptomatic congestive heart failure (class III and IV), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations would exclude patients from this study.
8. Contraindications to angiography and selective visceral catheterization: History of severe allergy or intolerance to any contrast media, or atropine. Bleeding diathesis, not correctable by usual forms of therapy that would include medical coagulopathy but not limited to the administration of blood products.
9. Nuclear Medicine scan demonstrates evidence of potential delivery of greater than 16.5 mCi (30 Gy absorbed dose) of radiation to the lungs with SIR-Sphere administration.
10. Evidence of any detectable Tc-99 MAA flow to the stomach or duodenum, after application of established angiographic techniques to stop such flow.
11. Utilization of capecitabine for the 6 weeks preceding SIR-Sphere therapy and indefinitely following SIR-Sphere therapy as per manufacturer's recommendations due to the increased risk of radiation hepatitis.