Inclusion Criteria:

- Age > 18 years

- Histological diagnosis of colorectal cancer that is KRAS wild type

- Metastatic disease not amenable to resection

- Measurable disease as assessed by CT scan using RECIST criteria

- Received and failed fluoropyrimidine therapy

- Received and failed oxaliplatin therapy

- Radiographically documented disease progression per RECIST criteria

- For phase 1b group only, ECOG PS 0-1

- For phase 2 group only, ECOG PS 0-2

- Adequate bone marrow function with haemoglobin > 100 g/L, platelets > 100 X 109/l;
neutrophils > 1.5 X 109/l within 7 days of enrolment

- Adequate renal function, with calculated creatinine clearance >40 ml/min (Cockcroft
and Gault) within 7 days of enrolment

- Adequate hepatic function with serum total bilirubin < 1.25 X upper limit of normal
range and ALT or AST<2.5xULN (<5xULN if liver metastases present) within 7 days of
enrolment

- Magnesium ≥ lower limit of normal within 7 days of enrolment.

- Fasting serum cholesterol ≤ 7.75mmol/L AND fasting triglycerides ≤ 2.5 x ULN. Note:
In case one or both of these thresholds are exceeded, the patient can only be
included after initiation of appropriate lipid lowering medication.

- Life expectancy of at least 12 weeks

- Negative pregnancy test ≤ 72 hours before commencing study treatment (women of
childbearing potential only).

- Written informed consent including consent for biomarker studies

Exclusion Criteria:

- Presence of KRAS mutation in tumour sample

- For Phase 1b group only, patients with prior pelvic radiotherapy.

- Systemic chemotherapy, immunotherapy, approved proteins/antibodies or any
investigational agent within 4 weeks prior to commencing study treatment

- Radiotherapy within 14 days of commencing study treatment.

- Unresolved toxicities from prior systemic therapy or radiotherapy

- Medical or psychiatric conditions that compromise the patient's ability to give
informed consent or to complete the protocol

- Prior treatment with drugs targeting EGFR such as cetuximab, panitumumab or erlotinib

- Prior therapy with mTOR inhibitors (sirolimus, temsirolimus, everolimus)

- Prior therapy with irinotecan

- CYP3A4 enzyme inducing anti-convulsant medication ≤ 14 days prior to study treatment.

- Ketoconazole ≤ 7 days before study treatment.

- Uncontrolled diabetes mellitus defined by fasting glucose >1.5 x ULN.

- Known cirrhosis, chronic active hepatitis, or chronic persistent hepatitis

- Patients with known interstitial lung disease or severely impaired lung function

- Patients with active bleeding diatheses.

- Any uncontrolled clinically significant cardiac disease, arrhythmias or angina
pectoris

- Active inflammatory bowel disease or other bowel disease causing chronic diarrhoea

- Chronic treatment with immunosuppressives

- Patients with a known history of HIV seropositivity

- Patients who have any severe and/or uncontrolled medical conditions or infections

- Untreated or symptomatic CNS metastases

- Patients who have a history of another primary malignant disease

- Pregnancy or lactation.

- Women and partners of women of childbearing potential who are not using effective
contraception.