FUDR/Oxaliplatin HAI Plus Irinotecan vs. FOLFOXIRI Chemotherapy in Treating Initially Unresectable CRCLM

Inclusion Criteria:

* Age ≥ 18 and ≤70.
* Diagnosed as colorectal adenocarcinoma by histology.
* Confirmed as liver metastases by medical imaging or pathology.
* MDT determined as unresectable liver metastases, defined as:①more than 5 metastases; ②unable to conduct R0 resection; ③no sufficient residual liver volume after resection; ④none of 3 hepatic vein can be reserved after resection, no sufficient blood supply or bibliary duct can be reserved, none of 2 adjacent liver segment can be reserved. Whenever meets any of the criteria mentioned above would be defined as unresectable liver metastases.
* No previous treatment aiming at treating liver metastases, including chemotherapy, surgery, radiotherapy, transcatheter hepatic arterial chemoembolization(TACE) or target therapy.
* Confirmed by CT, MRI or PET/CT(if necessary) that there is no extrahepatic metastases or only oligos extrahepatic metastases(no more than 2 organs and 5 leisions, maximum diameters of single leision ≤ 1cm).
* Unsuitable for cetuximab treatment(RAS mutation, unable to afford the cost).
* No hematologic dysfunction(Platelets \>90×10\^9/L; WBC \>3×10\^9/L; Neutrophil \>1.5×109/L).
* Serum bilirubin ≤ 1.5 × ULN; aminotransferase ≤ 5 × ULN.
* No ascites; no coagulation dysfunction; albumin ≥ 30g/L.
* Hepatic function was classified as class A by Child-Pugh classification.
* Serum creatinine \< 1 × ULN, or creatinine clearance rate(CCR) \> 50ml/min(calculated by Cockcroft-Gault formula).
* ECOG scored as 0-1.
* Life expectancy \> 3 months.
* Informed consent.
* Willing and able to receive follow-up until death or trial is finished or trial is terminated.

Exclusion Criteria:

* Presence of extensive extrahepatic metastases(more than 2 organs and 5 leisions, or maximum diameter of single leision \> 10 cm).
* Severe arterial embolism or ascites.
* Presence of hemorrhagic tendency or coagulation dysfunction.
* Presentive of hypertensive crisis or hypertensive encephalopathy.
* Severe uncontrolled systemic complications, such as infection or diabetes.
* Severe clinical CVD(cardiovascular disease), such as cerebrovascular accident(within 6 months before recruitment), myocardial infarction(within 6 months before recruitment), uncontrolled hypertension; unstable angina pectoris; congestive heart-failure(NYHA 2-4 grade); arrhythmia that needs medication treatment.
* Previous diagnosed or physical examination showed presence of central nervous system(CNS) disease(i.e. primary brain tumor, epilepsy uncontrolled by standard treatment, any history of brain metastases or stroke).
* Previous history of other malignancy within 5 years(except basal cell carcinoma after radical resection and/or cervical carcinoma in situ).
* Received any medication under research within 28 days before the trial.
* Any residual toxicity of previous chemotherapy(except hair loss), i.e. peripheral neuropathy ≥ NCI CTC v3.0 Grade 2, will be excluded from oxaliplatin-based chemotherapy regimen research pair.
* Allergic to any medication involved in the trial.
* Pregnant and lactating women.
* Patient who does not use or refuses to take any appropriate contraceptive measures (intrauterine contraceptive ring, barrier contraception combined with spermicidal gel or sterilization operation), including women of childbearing age (within 2 years after the last menstrual period) and men who are with possible fertility.
* Unable or unwilling to comply with the research plan.
* The existence of any other disease, dysfunction caused by metastatic lesions, or suspicious disease found on the regular examination, which indicating contraindications to the use of study drugs or may bring high risks of treatment related complications