"Our stockholders heard that we were involved in a process and they made it very clear that they did not want us to buy that company. So, very specifically, we had to walk away," he said in an interview with "Closing Bell."
"I love the CEO. I love the company. I love the brand. I love everything about Twitter but our stockholders don't and I listen to them. They are an important part of our family and how we do business at Salesforce."
That means that there is no price where a deal would make sense, unless shareholders had a change of heart, Benioff said.
Last week, Salesforce said it was ruling out a bid for the social media company. The news initially sent Salesforce shares higher, and Twitter shares tumbling. On Friday, Salesforce was up almost 2 percent.
In May, the company weighed 14 possible acquisition targets alone, including LinkedIn and Adobe Systems, according to The Wall Street Journal. The list of potential targets was in leaked emails of Salesforce board member and former Secretary of State Colin Powell.
Benioff told CNBC the company looks at a lot of things, but walks away from almost all of them.
"Only the very, very best assets are the ones that we are going to acquire," he said. "We have a very disciplined, refined, controlled process and we've made some very good decisions over the last several years in acquisitions."
And the reasons those transactions are made is because the company is always looking to innovate, he added.
"We're very committed to organic innovation, that is building new things ourselves, but we're also very committed to inorganic innovation, be able to bring amazing entrepreneurs and technology into our company and the M&A process is critical to doing that."
—CNBC's Julia Boorstin and Reuters contributed to this story.