## 1 Introduction  
Colorectal cancer (CRC) accounted for 9.39% of deaths by cancers in 2020 and is the third most commonly diagnosed cancer in the word. CRC incidence could double by 2035 due to an increase in the number of cases and their early diagnosis [1]. Current treatment is based on resection combined with chemotherapy and adjuvant radiotherapy in the early stages and larger resections that are associated with chemotherapy (oxaliplatin, irinotecan, 5-fluorouracilacil (5-FU) and capecitabine, among others) in metastatic stages [2]. However, despite the use of different therapeutic options, the average survival in metastatic patients is low (3 years) although the 5-year survival rates of patients that are diagnosed with localized tumors or with regional dissemination are 90% and 69%, respectively [3, 4]. Acquired or intrinsic drug resistance in CRC is one the main causes of treatment failure. A clinical assay that was performed with patients from 13 European countries, Israel, and South Africa showed that more than 50% of CRC patients had resistance to the drug 5-FU [5, 6]. In addition, the mechanisms that generate resistance to one drug produce resistance to others (multidrug resistance or MDR). The mechanism that is mediated by the ATP-dependent transporter family (ATP-binding cassette family, ABC) is prominent in CRC, including the p-glycoprotein (p-GP; ABCB1), a drug efflux pump which prevents cellular uptake of many structurally and functionally cytotoxic compounds [7, 8]. Understanding resistance phenomena is essential for improving CRC patient prognosis.  
In this context, it has been shown that some plant-derived natural products or their association with the classic cytotoxic drugs used in cancer treatment were capable of overcoming multidrug resistance and/or reducing the effective antitumor drug dose [9].  
Despite the low proportion of plant species that have been explored for their antitumor activity [10], plant-derived natural products have played an important role in the treatment and prevention of cancer. Most of the compounds from vegetables and fruits with significant antitumor activity also showed clear advantages in relation to modern drugs that are used in chemotherapy [11]. Furthermore, this therapeutic strategy based on the use of natural compounds showed minimal side effects and lower cost than synthesized antitumor drugs [12]. However, biodistribution, biotransformation, and transport limitations of natural products may hinder their application in cancer patients. Furthermore, their effect on the immune system is not fully analyzed [13; 14; 15]. Concretely in CRC, the therapeutic potential of some natural compounds has been clearly demonstrated [16]. In addition, their combination with other conventional chemotherapeutic drugs has demonstrated a significant synergistic effect [17]. In fact, curcumin, resveratrol, and (-)-Epigallocatechin Gallate (EGCG) and terpenoids, secondary plant metabolites that are composed of isoprene units, enhanced the effect of cytotoxic drugs [18; 19; 20]. The antitumor effect exerted by these compounds is carried out through several pathways including cell cycle arrest and cell death by apoptosis [21]. On the other hand, polyphenols from plants also prevent multidrug resistance in several types of solid tumors, including CRC. In addition, these compounds inhibit cell proliferation, angiogenesis, and metastasis, as well as regulating the proinflammatory response [22]. Finally, quercetin, a flavonoid, not only modulates the drug resistance phenomena but is capable of increasing sensitivity to doxorubicin in CRC through the inhibition of a glutamine transporter (SLC1A5) [23; 24].  
The objective of this review is to study the different families of plant-derived compounds that modulate drug resistance in CRC, observing their ability to be used as a future therapy against this type of cancer.