The aim of this clinical trial is to find out whether Regorafenib and Sintilimab in combination with electroacupuncture works in treating participants with microsatellite stable (MSS) advanced colorectal cancer who have failed one or more second-line standard chemotherapy regimens. It will also learn about the efficacy and safety of the combination therapy. The main questions the trial aims to answer are:

Does combination therapy reduce the overall survival time ? What medical problems do people have when they take combination therapy?

Participants will

Regorafenib, take for 2 weeks and stop for 1 week; Sintilimab, intravenous, every 3 weeks; Electroacupuncture was performed 1 day before, on the day of, and on the 2nd day after each cycle of Sintilimab administration, and patients completed 3 treatments in week 1, followed by 1 treatment per week for 2 weeks, with 5 treatments per dosing

Inclusion Criteria:

1. Fullly knowledge of the study and voluntarily sign the informed consent;
2. Histologically and/or cytologically confirmed metastatic colorectal adenocarcinoma (Stage IV) with microsatellite stable (MSS)* confirmed by PCR or NGS;
3. Receive at least two lines of standard chemotherapy in the past and have failed.
4. No systemic chemotherapy or antitumor therapy such as radiotherapy, immunotherapy, biological or hormonal therapy in the past 4 weeks; and have never received VEGFR inhibitors
5. Willing to receive electroacupuncture;
6. Aged 18-75 years old (including 18 years old and 75 years old);
7. Weighing more than 40 kg (including 40 kg);
8. Able to take oral medication.
9. Patients with adequate organ function at the time of enrollment are defined as follows: Neutrophil count ≥1500mm3 Platelet count ≥10.0 × 104/mm3 Hemoglobin (Hb) ≥ 9 g/dL Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤100 U/L (≤100 U/L in patients with hepatocellular carcinoma, ≤250 U/L in patients with liver metastasis) Total bilirubin ≤1.5 mg /dL Creatinine ≤1.5 mg /dL Lipase ≤ 80 IU/L Urine Protein: one of the following (if any of the criteria are met, no other test may be performed) (i) Urine Protein (paper test) of 2+ or less (ii) UPC < 3.5 (iii) Urine Protein ≦ 3500 mg for 24 hour urine protein measurements. mg Prothrombin time (PT)-International Normalized Ratio (INR): ≤ 1.5 (≤ 3.0 for anticoagulant administration)
10. Eastern Cooperative Oncology Group Physical Performance Score (ECOG PS) ≤ 1 (0-1);
11. Cardiac function evaluation: left ventricular ejection fraction ≥ 50% (echocardiography);
12. Clearly meet the criteria for evaluating the efficacy of solid tumors (e.g., echocardiograms) Measurable lesions that meet the requirements of RECIST 1.1;
13. Expected survival of more than 12 weeks.

Exclusion Criteria:

Patients will be excluded from the study if any of the following criteria are met.

1. Patients who have received systemic chemotherapy, radiotherapy, surgery, hormonal therapy or immunotherapy <2 weeks prior to enrolment. Immune checkpoint blockade pretreatment is permitted.
2. Patients with a history of regorafenib administration.
3. Patients with uncontrolled hypertension (systolic blood pressure ≥160 mmHg and diastolic blood pressure ≥90 mmHg) despite multiple antihypertensive medications; and
4. Patients with acute coronary syndromes (including myocardial infarction and unstable angina) and a history of coronary angioplasty or stenting within 6 months prior to enrolment;
5. Patients with a large pleural effusion or ascites requiring drainage; and
6. Patients with grade ≥ 3 active infection according to NCI CTC AE version 4.03; patients with symptomatic brain metastases; and patients with a history of coronary artery angioplasty or stenting within the previous 6 months.
7. Patients with symptomatic brain metastases;
8. Patients with partial or complete gastrointestinal obstruction;
9. Patients with interstitial lung disease with active signs or symptoms;
10. Patients who test positive for anti-HIV-1 antibody, anti-HIV-2 antibody, hepatitis B surface antigen (HBsAg), or anti-hepatitis C virus (HCV)* *Patients who test positive for anti-hepatitis B surface (HBs) or anti-hepatitis B core (HBc) antibodies and patients with hepatitis B virus (HBV)-DNA measurements that are greater than the sensitivity of the test will also be excluded. Patients with concurrent autoimmune disease
11. Patients with concurrent autoimmune disease or a history of chronic or recurrent autoimmune disease.
12. Patients requiring systemic corticosteroids (excluding those given temporarily for testing, prophylactic administration for allergic reactions, or for the relief of swelling associated with radiotherapy) or immunosuppressive agents, or who have received such therapy <14 days prior to study participation;
13. Patients with a history or finding of class ≥III congestive heart failure according to the New York Heart Association functional class;
14. Patients with epilepsy requiring pharmacological treatment;
15. Patients with grade 3 or greater bleeding within 4 weeks prior to enrolment.
16. Patients who have undergone major surgery (open heart or caesarean section, etc.), caesarean biopsy, or trauma within 28 days prior to enrolment. the same day of the week prior to the 4-week period may be enrolled (however, in the case of manual anastomosis without bowel resection, this should be within 14 days prior to enrolment);
17. Patients with non-healing wounds, non-healing ulcers or non-healing fractures.
18. Patients with a history of hypersensitivity reaction to any investigational drug, analogue or excipient.
19. Women who are pregnant or breastfeeding or have the potential to become pregnant.
20. Patients with contraindications to electroacupuncture therapy or patients for whom electroacupuncture is contraindicated in accordance with TCM syndromes.