(1) Evaluate the efficacy of apatinib in combination with standard second-line chemotherapy for advanced colorectal cancer. Whether it can prolong Progression Free Survival (PFS), overall survival (OS) in patients with advanced colorectal cancer and reduce symptoms and improve quality of life compared with standard second-line chemotherapy; (2) Observe the safety of apatinib for the treatment of advanced colorectal cancer.

Standard second line chemotherapy includes chemotherapy based on irinotecan or chemotherapy based on oxaliplatin.

Apatinib is a small-molecule tyrosine kinase inhibitor (TKI) that highly selectively binds to and strongly inhibits vascular endothelial growth factor receptor 2 (VEGFR-2), with a decrease in VEGF-mediated endothelial cell migration, proliferation, and tumor microvascular density. A phase II trail of Apatinib has been demonstrated that Apatinib is safe to treat the metastatic colorectal cancer and the disease control rate can reach 50%.

Inclusion Criteria:

1. Male or female aged 18 to 70 years old;

2. Histologically or cytologically proven patients with metastatic colorectal cancer have undergone a first-line standard regimen recommended by the NCCN guidelines for progression;

3. According to the RECIST 1.1 criteria, the patient has at least one target lesion that can measure the diameter;

4. ECOG PS ≤ 2;

5. Expected survival time of more than 12 weeks.

6. The level of organ function must meet the following requirements:

   Bone marrow: neutrophil count (ANC) ≥ 1.5 × 10^9/L, platelet ≥ 75 × 10^9/L, hemoglobin ≥ 90g/L.

   Liver: serum bilirubin ≤ 2 times the upper limit of normal, aminotransferase AST and ALT ≤ 2.5 times the normal upper limit.

   Kidney: Serum creatinine ≤1.5 times upper limit of normal.

7. Patient compliance is good;

8. Understand and voluntarily sign a written informed consent.

Exclusion Criteria:

1. Other previous or concurrent malignancy, except cured skin basal cell carcinoma and cervical carcinoma in situ;
2. Already known to be allergic to apatinib or any excipient;
3. Use unapproved drugs or other test medications within 4 weeks prior to enrollment;
4. There are many factors that affect oral medications (such as inability to swallow, chronic diarrhea and intestinal obstruction);
5. Patients with a history of CNS metastases or CNS metastases;
6. A history of bleeding, with any serious grading within 4 weeks prior to screening reaching a bleeding event of 3 degrees Celsius or greater in CTCAE4.0;
7. Serious infection;
8. Serious cardiovascular disease: uncontrolled hypertension, unstable angina, grade 3-4 heart failure (NYHA standard), congestive heart failure;
9. urinary routine urinary protein ≥ ++ and confirmed 24-hour urinary protein quantitation> 1.0 g;
10. Within 30 days after major surgery;
11. Thrombotic disease. Anemia or venous thrombosis occurred in the previous year, such as cerebrovascular accident (including transient ischemic attack), deep vein thrombosis, pulmonary embolism, etc.;
12. Those with history of psychotropic substance abuse who can not be abstinent or have mental disorders;
13. Have clinical symptoms, need clinical intervention pleural effusion or ascites;
14. At the investigator's discretion, there is a serious concomitant condition that compromises the patient's safety or affects the patient in completing the study.