Inclusion Criteria:

• Histological or cytological proof of colon or rectal adenocarcinoma
• Measurable site of disease according to RECIST that has not been previously irradiated
• Must have metastatic colorectal cancer which progressed after first line chemotherapy +/- bevacizumab
• Blood sample collected within 21 days prior to being registered for protocol therapy for UTG1A1 genotype analysis. (Patients with the UGT1A1 *28 7/7 genotype (homozygosity for the TA7 allele) will be excluded from the Phase I stage of the study. During the Phase II stage of the study, subjects will be allowed to participate but must begin treatment at dose level -1 of irinotecan.)
• A history of other malignancies (non-colorectal) is allowed, provided it has been curatively treated and demonstrates no evidence for recurrence of that cancer
• Prior radiation therapy allowed to < 25% of the bone marrow
• Age ≥ 18 years at the time of consent
• Written informed consent and HIPAA authorization for release of personal health information
• Females of childbearing potential and males must be willing to use an effective method of contraception
• Females of childbearing potential must have a negative pregnancy test within 7 days of being registered for protocol therapy

Exclusion Criteria:

• No more than one prior chemotherapy regimen for metastatic colorectal cancer, at least 28 days prior to being registered for protocol therapy
• No prior treatment with cetuximab
• No prior treatment with an mTOR inhibitor
• No known hypersensitivity to cetuximab, RAD001 (everolimus), other rapamycins (sirolimus, temsirolimus) or to its excipients
• No treatment with any investigational agent within 28 days prior to being registered for protocol therapy
• No symptomatic brain metastasis
• No uncontrolled diabetes as defined by a fasting serum glucose >1.5 x ULN
• No chronic treatment with systemic steroids or another immuno-suppressive agent
• No serious non-healing wound, ulcer, bone fracture, major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to being registered for protocol therapy
• No liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis
• No active bleeding or a pathological condition that is associated with a high risk of bleeding
• No uncontrolled systemic disease including active infections or uncontrolled hypertension
• No known history of HIV seropositivity
• No impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
• No nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with protocol therapy
• No planned immunization with attenuated live viruses during the study period
• Females must not be breastfeeding