Previous OPTIMOX1 study investigated the use of oxaliplatin discontinuation and reintroduction in a novel stop-and-go strategy. Previously untreated patients were randomly assigned to either FOLFOX4 administered every 2 weeks until progression (arm A) or FOLFOX7 for 6 cycles, maintenance without oxaliplatin for 12 cycles, and reintroduction of FOLFOX7 for another 6 cycles (arm B). Data showed that there was no significant difference in median progression-free survival (PFS) and overall survival (OS) between two arms. Furthermore, this study showed lower Grade 3 neurotoxicity rate in arm B (17.9% vs 13.3%, P = 0.12).In order to investigate the efficacy and feasibility of the novel "Stop and go" strategy in Chinese mCRC patients, Prof. Shu Yongqian in JiangShu Province Hospital plans to conduct a randomized controlled study to compare continuous FOLFOX4 vs. FOLFOX4 in a Stop-and-Go Fashion in 1st Line mCRC patients. To avoid the high oxaliplatin dosage related neurotoxicity, FOLFOX4 regimen is chosen in this study.

Inclusion Criteria:

• Patients with histologically confirmed adenocarcinoma of the colon or rectum
• Unresectable metastases
• At least one bidimensionally measurable lesion of ≥ 1 cm
• No previous chemotherapy for metastatic disease; Completed at least more than 1 year oxaliplatin therapy for adjuvant treatment
• 18-75 years old
• ECOG 0-2
• Life expectancy greater than 3 months
• Hemogram: WBC≥4.0 X109/L, ANC ≥2 X109/L, PLT ≥100 X109/L, Hb ≥90g/L,
• Adequate Renal Function
• Adequate Liver Function
• Signed informed consent before the treatment

Exclusion Criteria:

• Patients with previous oxaliplatin based adjuvant chemotherapy within 1 Year
• Completely or partially bowel obstruction
• Presence of peripheral neuropathy (CTC>grade I)
• Severe mental disorder
• CNS metastasis
• With other severe disease: uncontrolled active infectious disease, uncontrolled hypertension, heart infarction within 1 year, uncontrolled high-risk arrhythmia, unstable angina
• With other malignant disease previously or concurrently
• Receive other anti-tumor treatment
• Pregnant or lactating women, or women of child bearing potential without contraceptive method.