Colorectal cancer will be resistant to Chemotherapy drugs after treated for a period of time .In the past, the classical treatment regiment was to change other drug after tumor progressed. In theory, the continuous use of such a drug could shortening the patient's drug resistance time. It has been shown that the alternate use of the two drug combinations is reasonable in clinical. This application can not only further improve the curative effect but also significantly reduce the side effects. So the investigators are going to carry out a prospective phase II clinical study. The control group change to second-line treatment after progression of first-line drugs. The experimental group use the first line and the second line,alternately, for every two cycles. The combination of bevacizumab is a first line development, and the second line can still be used .Objective to compare the clinical value of XELOX and XELIRI alternation regimen in the first-line treatment of advanced colorectal cancer.

Inclusion Criteria:

1. Diagnosed as colorectal adenocarcinoma by histopathology and/or cytology.

2. Patients could not receive surgical resection.

3. Never received chemotherapy or radiotherapy.

4. According to the RECIST v1.1 guide, at least 1 lesions (never received radiotherapy),accurately measured by computed tomography (CT) or magnetic resonance imaging (MRI) (intravenous contrast agent as the first choice),the longest diameter was more than 10mm (except for the lymph nodes, the short axis of the lymph nodes must be more than 15mm), repeated measurement.

5. Eastern Cooperative Oncology Group Performance Status(ECOG PS):0-1 score

6. The main organs function is normal, which meets the following requirements. (1) Blood routine examination,(no blood transfusion within 14 days).

   1. Hemoglobin(HB)≥90g/L;
   2. Absolute neutrophil count (ANC) ≥1.5×10^9/L;
   3. Blood platelet (PLT)≥80×10^9/L; (2) Biochemical examination should comply with the following criteria:
   1. Bilirubin(BIL) <1.5 times of the upper limit of normal value (ULN)
   2. Alanine aminotransferase (ALT) and aspartate aminotransferase(AST)<2.5*ULN (liver metastasis ALT and AST<5*ULN).
   3. Serum Cr≤1*ULN, creatinine clearance rate≥50ml/min(Cockcroft-Gault formula)

7. The expected survival time more than 3 months;

8. The physicians plan to use XELOX chemotherapy or XELIRI chemotherapy.

9. Patients voluntarily joined the study and signed informed consent form(ICF).

10. Childbearing age women must undergo a negative pregnancy test(serum or urine) within 7 days ,and voluntarily adopt appropriate methods for contraception from the period of under observation and within 8 weeks of the last time they are given the drug;As for men, it is necessary to receive surgical sterilization, or agree to adopt appropriate methods for contraception from the period of under observation and within 8 weeks of the last time they are given the drug.

Exclusion Criteria:

1. There is a case of heart disease in any of the following situations. (1)Recent publications have the following heart disease (within 6 months)

   1. Acute coronary artery syndrome

   2. Acute heart failure (grade III or IV of NYHA classification)

   3. Significant ventricular arrhythmia(sustained ventricular tachycardia, ventricular fibrillation and sudden death after resuscitation).

      (2)The New York Heart Association(NYHA) grade of grade III or IV (3)The patients with severe conduction block, and permanent pacemaker is invalid (two degree and three degree atrioventricular block, sinus arrest) (4)Unexplained syncope occurred within 3 months.

      (5)The researchers identified as uncontrol of severe hypertension, or symptomatic hypertension.

2. There are many factors that affect the absorption of oral drugs (such as unable to swallow, nausea and vomiting, chronic diarrhea and intestinal obstruction).

3. ECOG score≥2

4. Abnormal coagulation function (INR>1.5*ULN, Activated Partial Thromboplastin Time (APTT)>1.5*ULN), with bleeding tendency.

5. There is any history of allergy or hypersensitivity in this research's drug or adjuvant.

6. HIV infection and/or active hepatitis B virus infection.

7. Any condition that may damage the safety of patients or the integrity of research data, including serious medical risk factors, physical condition and laboratory abnormality.

8. The high risk population carrying UGT1A1*28 (7/7) *6 (A/A) genotype or simultaneous carrying of the UGT1A1*28 (6/7) *6 (A/G) genotype (the heterozygous genotype) suggests the exclusion of the Irinotecan

9. Pregnant or lactating women;

10. Other conditions which the doctor think not suitable for inclusion.