Inclusion Criteria:
* Histologically/cytologically confirmed diagnosis of moderate or poorly differentiated appendiceal or colorectal adenocarcinoma of any grade with Initial resectable disease.
* Have metastatic peritoneal disease that is visible on imaging or at the time of laparoscopy.
* Age ≥18 years. Because no adverse event data are currently available on the use of ctDNA in chemotherapy decision making in patients \<18 years of age, children are excluded from this study.
* ECOG performance status ≤1 (Karnofsky ≥70%,).
* Patients must have adequate organ and marrow function as defined below:
absolute neutrophil count ≥1,000/mcL platelets ≥100,000/mcL total bilirubin 1.5x ≤ institutional upper limit of normal (ULN) AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN Creatinine clearance ≥30 mL/min
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
* Patients with treated brain metastases are not eligible.
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better.
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
* Estimated life-expectancy of \> 4 months.
* The effects of standard chemotherapeutic agents used in this trial (5-fluouracil, oxaliplatin, leucovorin, and irinotecan) on the developing human fetus are detrimental. For this reason and because these agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. (Refer to Pregnancy Assessment Policy MD Anderson Institutional Policy # CLN1114). This includes all female patients, between the onset of menses (as early as 8 years of age) and 55 years unless the patient presents with an applicable exclusionary factor which may be one of the following:
* Postmenopausal (no menses in greater than or equal to 12 consecutive months).
* History of hysterectomy or bilateral salpingo-oophorectomy.
* Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy).
* History of bilateral tubal ligation or another surgical sterilization procedure.
* Approved methods of birth control are as follows: Hormonal contraception (i.e., birth control pills, injection, implant, transdermal patch, vaginal ring), Intrauterine device (IUD), Tubal Ligation or hysterectomy, Subject/Partner post vasectomy, Implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
* Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of their chemotherapy administration.
* Ability to understand and the willingness to sign a written informed consent document.
* English and Non-English-speaking.
Exclusion Criteria:
* Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> Grade 1) with the exception of alopecia.
* Patients who are receiving any other investigational agents.
* Patients with brain or other visceral (i.e. liver and/or lung) metastases at the discretion of the investigator.
* Patients with uncontrolled intercurrent illness (Indicate clearly what type or extent)
* Patients with psychiatric illness/social situations that would limit compliance with study requirements.
* Pregnant women are excluded from this study because chemotherapeutic agents used carry the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with chemotherapy, breastfeeding should be discontinued if the mother is treated with chemotherapy. These potential risks may also apply to other agents used in this study.
* If participant received major surgery within last 4 weeks, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
* Serious adverse chemotherapy related adverse events (grade 3 or 4) that were symptomatic and required prolong chemotherapy break (\>6weeks).
* Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the study subject's best interest to participate, in the opinion of the treating investigator.
