This is a prospective randomized phase II trial was done in clinical oncology department at Kasr Alainy hospital, Cairo university (NEMROCK) to evaluate the role of intensification of chemotherapy in the first line for treatment of metastatic colorectal carcinoma by adding third agent to standard doublet regimen on oncological outcomes & assess tolerance to the intensified treatment

Patients with histologically proven adenocarcinoma of the colon or rectum, with unresectable measurable metastatic disease, were enrolled and randomized in a 1:1 ratio.

Patients were assigned to receive FOLFOXIRI (experimental arm) or FOLFIRI or FOLFOX4 (control arm) biweekly up to 12 cycles.

Randomization was done by enclosed envelope method Evaluation of the patients for surgical resection of residual metastases was done every 12 weeks. In the case of secondary resection of metastases, patients completed with the same chemotherapy regimen received before resection up to 12 cycles Maintenance therapy with capecitabine for 6 months was administered for patients who achieved complete or partial tumor response. In case of disease progression, second line chemotherapy was then administered in both groups until tumor progression, the occurrence of an unacceptable adverse event, or patient refusal

Inclusion Criteria:

• Patients with histologically proven adenocarcinoma of the colon or rectum, with unresectable measurable metastatic disease
• No previous treatment for the metastatic disease was allowed, only previously fluoropyrimidine-based adjuvant chemotherapy was allowed if ended more than 6 months before enrollment in the study
• Adequate haematological parameters (leukocyte count of at least 3,500/mm₃, neutrophil count of at least 1,500/ mm and platelet count of at least 100,000/mm
• Adequate liver and renal function parameters (serum creatinine ≤ 1.3 mg/dL, serum bilirubin ≤ 1.5 mg/dL and AST, ALT and alkaline phosphatase 2.5 x upper normal values or less.
• Patient had no co-morbidity disease

Exclusion Criteria:

• Poor performance status 3-4 according to ECOG score, prior chemotherapy for advanced, recurrent or metastatic disease, other simultaneous malignancies and pregnant or lactating female